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    GCN4 amino acid starvation-responsive transcription factor GCN4 [ Saccharomyces cerevisiae S288C ]

    Gene ID: 856709, updated on 9-Dec-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Differential stability of Gcn4p controls its cell-specific activity in differentiated yeast colonies.

    Differential stability of Gcn4p controls its cell-specific activity in differentiated yeast colonies.
    Váchová L, Plocek V, Maršíková J, Rešetárová S, Hatáková L, Palková Z., Free PMC Article

    06/5/2024
    Multiomics of GCN4-Dependent Replicative Lifespan Extension Models Reveals Gcn4 as a Regulator of Protein Turnover in Yeast.

    Multiomics of GCN4-Dependent Replicative Lifespan Extension Models Reveals Gcn4 as a Regulator of Protein Turnover in Yeast.
    Mariner BL, Felker DP, Cantergiani RJ, Peterson J, McCormick MA., Free PMC Article

    11/29/2023
    Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan.

    Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan.
    Gulias JF, Niesi F, Arán M, Correa-García S, Bermúdez-Moretti M., Free PMC Article

    11/2/2023
    Stochastic scanning events on the GCN4 mRNA 5' untranslated region generate cell-to-cell heterogeneity in the yeast nutritional stress response.

    Stochastic scanning events on the GCN4 mRNA 5' untranslated region generate cell-to-cell heterogeneity in the yeast nutritional stress response.
    Meng X, Reed A, Lai S, Szavits-Nossan J, McCarthy JEG., Free PMC Article

    07/26/2023
    Origin of translational control by eIF2alpha phosphorylation: insights from genome-wide translational profiling studies in fission yeast.

    Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast.
    Asano K., Free PMC Article

    09/4/2021
    Mediator subunit Med15 dictates the conserved ""fuzzy"" binding mechanism of yeast transcription activators Gal4 and Gcn4.

    Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4.
    Tuttle LM, Pacheco D, Warfield L, Wilburn DB, Hahn S, Klevit RE., Free PMC Article

    05/1/2021
    Genome-scale reconstruction of Gcn4/ATF4 networks driving a growth program.

    Genome-scale reconstruction of Gcn4/ATF4 networks driving a growth program.
    Srinivasan R, Walvekar AS, Rashida Z, Seshasayee A, Laxman S., Free PMC Article

    01/23/2021
    ln4p depletion reduces this sequestration capacity, allowing uncharged tRNAGln to interact with Gcn2 kinase. The study sheds new light on mutant aaRS disease aetiologies, and explains how aaRS sequestration of uncharged tRNAs can prevent GCN4 activation under non-starvation conditions.

    The molecular aetiology of tRNA synthetase depletion: induction of a GCN4 amino acid starvation response despite homeostatic maintenance of charged tRNA levels.
    McFarland MR, Keller CD, Childers BM, Adeniyi SA, Corrigall H, Raguin A, Romano MC, Stansfield I., Free PMC Article

    05/23/2020
    eIF2beta or eIF1 substitutions disrupting these contacts increase initiation at UUG codons, and compound substitutions also derepress translation of GCN4, indicating slower TC recruitment.

    A network of eIF2β interactions with eIF1 and Met-tRNAi promotes accurate start codon selection by the translation preinitiation complex.
    Thakur A, Marler L, Hinnebusch AG., Free PMC Article

    10/19/2019
    Authors find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity.

    Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.
    Tuttle LM, Pacheco D, Warfield L, Luo J, Ranish J, Hahn S, Klevit RE., Free PMC Article

    09/21/2019
    These findings suggest that Ssb2 is a critical factor that modulates Gcn4 functions in the nucleus and cytosol.

    Ssb2 is a novel factor in regulating synthesis and degradation of Gcn4 in Saccharomyces cerevisiae.
    Jung Y, Seong KM, Baek JH, Kim J.

    07/20/2019
    Met4, Ino2, and Gcn4 have been shown to have similar functions in transcription activation assays and to require Med15 for activation of Mediator tail-dependent promoters, and both ADs bind Med15 activator-binding domains with low micromolar affinities.

    Transcription Activation Domains of the Yeast Factors Met4 and Ino2: Tandem Activation Domains with Properties Similar to the Yeast Gcn4 Activator.
    Pacheco D, Warfield L, Brajcich M, Robbins H, Luo J, Ranish J, Hahn S., Free PMC Article

    05/18/2019
    Gcn4 sites within coding sequences can activate sub-genic and full-length transcripts from the same or adjacent genes, showing that functional Gcn4 binding is not confined to promoters.

    Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5' Promoters in Yeast.
    Rawal Y, Chereji RV, Valabhoju V, Qiu H, Ocampo J, Clark DJ, Hinnebusch AG., Free PMC Article

    02/9/2019
    Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2alpha, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator

    Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan.
    Hu Z, Xia B, Postnikoff SD, Shen ZJ, Tomoiaga AS, Harkness TA, Seol JH, Li W, Chen K, Tyler JK., Free PMC Article

    01/26/2019
    The overexpression of eIF1 improved expression of HIS4(AUG) allele and GCN4 transcript causing 3AT resistance, whereas overexpression of eIF1 resulted in diminished UUG codon recognition of HIS4(UUG) allele causing 3AT sensitivity, despite having higher GCN4 expression

    Fidelity of HIS4 start codon selection influences 3-amino-1,2,4-triazole sensitivity in GTPase activating protein function defective eIF5.
    Charles Antony A, Alone PV.

    12/22/2018
    GCN4 is required for the elevated life spans of nup100-null mutants, similar to other previously described tRNA export and ribosomal mutants.

    Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs.
    Lord CL, Ospovat O, Wente SR., Free PMC Article

    09/9/2017
    SCH9 deletion causes the upregulation of many amino acid biosynthesis pathways and increases glycerol during fermentation. When Gcn4p was overexpressed during winemaking, increased glycerol production was also observed.

    Sch9p kinase and the Gcn4p transcription factor regulate glycerol production during winemaking.
    Vallejo B, Orozco H, Picazo C, Matallana E, Aranda A.

    08/5/2017
    The down-regulation of the GCN4 expression (Gcn(-) phenotype) in the eIF5(G31R) mutant was not because of leaky scanning defects; rather was due to the utilization of upUUG initiation codons at the 5' regulatory region present between uORF1 and the main GCN4 ORF.

    Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation.
    Antony A C, Alone PV.

    06/24/2017
    GCN4 is required for nitrogen catabolite repression-sensitive nuclear Gln3 localization.

    General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization.
    Tate JJ, Buford D, Rai R, Cooper TG., Free PMC Article

    06/3/2017
    Gcn4 sumoylation in limiting its association with chromatin.

    Chromatin Association of Gcn4 Is Limited by Post-translational Modifications Triggered by its DNA-Binding in Saccharomyces cerevisiae.
    Akhter A, Rosonina E., Free PMC Article

    05/27/2017
    mms21RINGDelta mutant exhibits (1) reduced ribosomal RNA production; (2) nuclear accumulation of ribosomal proteins; (3) elevated Gcn4 translation, indicating translational stress; We identified RPL19A as a novel genetic suppressor of the mms21RINGDelta mutant; Deletion of a previously identified strong suppressor, MPH1, rescues both the accumulation of ribosome subunits and translational stress

    Mms21 SUMO Ligase Activity Promotes Nucleolar Function in Saccharomyces cerevisiae.
    Kim DH, Harris B, Wang F, Seidel C, McCroskey S, Gerton JL., Free PMC Article

    05/27/2017
    Presented are molecular dynamics simulations reflecting a secondary structure of phopspho-GCN4 at different pH.

    Nuclear Magnetic Resonance Structures of GCN4p Are Largely Conserved When Ion Pairs Are Disrupted at Acidic pH but Show a Relaxation of the Coiled Coil Superhelix.
    Kaplan AR, Brady MR, Maciejewski MW, Kammerer RA, Alexandrescu AT., Free PMC Article

    05/20/2017
    the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.

    A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.
    McCormick MA, Delaney JR, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, Chou AC, Ahmed U, Carr D, Murakami CJ, Schleit J, Sutphin GL, Wasko BM, Bennett CF, Wang AM, Olsen B, Beyer RP, Bammler TK, Prunkard D, Johnson SC, Pennypacker JK, An E, Anies A, Castanza AS, Choi E, Dang N, Enerio S, Fletcher M, Fox L, Goswami S, Higgins SA, Holmberg MA, Hu D, Hui J, Jelic M, Jeong KS, Johnston E, Kerr EO, Kim J, Kim D, Kirkland K, Klum S, Kotireddy S, Liao E, Lim M, Lin MS, Lo WC, Lockshon D, Miller HA, Moller RM, Muller B, Oakes J, Pak DN, Peng ZJ, Pham KM, Pollard TG, Pradeep P, Pruett D, Rai D, Robison B, Rodriguez AA, Ros B, Sage M, Singh MK, Smith ED, Snead K, Solanky A, Spector BL, Steffen KK, Tchao BN, Ting MK, Vander Wende H, Wang D, Welton KL, Westman EA, Brem RB, Liu XG, Suh Y, Zhou Z, Kaeberlein M, Kennedy BK., Free PMC Article

    09/10/2016
    Reinitiation on GCN4 mRNA after translation of its four short uORFs is regulated by the sequence immediately following their respective stop codons.

    In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs.
    Gunišová S, Beznosková P, Mohammad MP, Vlčková V, Valášek LS., Free PMC Article

    08/13/2016
    coordinated sumoylation of Gcn4, Tup1 and likely other factors dampens activated transcription by stabilizing Tup1 binding and stimulating Gcn4 and RNAP II removal

    Sumoylation controls the timing of Tup1-mediated transcriptional deactivation.
    Ng CH, Akhter A, Yurko N, Burgener JM, Rosonina E, Manley JL., Free PMC Article

    08/15/2015
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